tbuckley/cabot-search huggingface dataset:
Decompressive Craniectomy versus Craniotomy for Acute Subdural Hematoma
Authors: Peter J. Hutchinson, Hadie Adams, Midhun Mohan, Bhagavatula I. Devi, Christopher Uff, Shumaila Hasan, Harry Mee, Mark H. Wilson, Deepak K. Gupta, Diederik Bulters, Ardalan Zolnourian, Catherine J. McMahon, Matthew G. Stovell, Yahia Z. Al-Tamimi, Manoj K. Tewari, Manjul Tripathi, Simon Thomson, Edoardo Viaroli, Antonio Belli, Andrew T. King, Adel E. Helmy, Ivan S. Timofeev, Sarah Pyne, Dhaval P. Shukla, Dhananjaya I. Bhat, Andrew R. Maas, Franco Servadei, Geoffrey T. Manley, Garry Barton, Carole Turner, David K. Menon, Barbara Gregson, Angelos G. Kolias
Journal: New England Journal of Medicine (2023)

Traumatic acute subdural hematomas frequently warrant surgical evacuation by means of a craniotomy (bone flap replaced) or decompressive craniectomy (bone flap not replaced). Craniectomy may prevent intracranial hypertension, but whether it is associated with better outcomes is unclear. Download a PDF of the Research Summary. We conducted a trial in which patients undergoing surgery for traumatic acute subdural hematoma were randomly assigned to undergo craniotomy or decompressive craniectomy. An inclusion criterion was a bone flap with an anteroposterior diameter of 11 cm or more. The primary outcome was the rating on the Extended Glasgow Outcome Scale (GOSE) (an 8-point scale, ranging from death to "upper good recovery" [no injury-related problems]) at 12 months. Secondary outcomes included the GOSE rating at 6 months and quality of life as assessed by the EuroQol Group 5-Dimension 5-Level questionnaire (EQ-5D-5L). A total of 228 patients were assigned to the craniotomy group and 222 to the decompressive craniectomy group. The median diameter of the bone flap was 13 cm (interquartile range, 12 to 14) in both groups. The common odds ratio for the differences across GOSE ratings at 12 months was 0.85 (95% confidence interval, 0.60 to 1.18; P=0.32). Results were similar at 6 months. At 12 months, death had occurred in 30.2% of the patients in the craniotomy group and in 32.2% of those in the craniectomy group; a vegetative state occurred in 2.3% and 2.8%, respectively, and a lower or upper good recovery occurred in 25.6% and 19.9%. EQ-5D-5L scores were similar in the two groups at 12 months. Additional cranial surgery within 2 weeks after randomization was performed in 14.6% of the craniotomy group and in 6.9% of the craniectomy group. Wound complications occurred in 3.9% of the craniotomy group and in 12.2% of the craniectomy group. Among patients with traumatic acute subdural hematoma who underwent craniotomy or decompressive craniectomy, disability and quality-of-life outcomes were similar with the two approaches. Additional surgery was performed in a higher proportion of the craniotomy group, but more wound complications occurred in the craniectomy group. (Funded by the National Institute for Health and Care Research; RESCUE-ASDH ISRCTN Registry number, ISRCTN87370545.) QUICK TAKE VIDEO SUMMARYCraniectomy vs. Craniotomy for Acute Subdural Hematoma 01:43
Traumatic Acute Subdural Hematoma — Should the Bone Flap Be Removed or Replaced?
Authors: Shankar Gopinath
Journal: New England Journal of Medicine (2023)

Traumatic acute subdural hematomas often warrant emergency evacuation of the blood clot to avoid further cerebral compression and its sequelae. Once the subdural clot is removed, the million-dollar question in the mind of the neurosurgeon is to whether to replace the bone flap (craniotomy) or not (decompressive craniectomy). In some instances, the decision to leave the bone flap on or off is relatively straightforward, such as in older persons with atrophic brains who have a visually "relaxed" brain after clot evacuation (in whom the bone flap should be replaced) or in a patient with massively swollen brain (in whom the . . .
Hypoxia hits APOL1 in the kidney
Authors: Steffen Grampp, René Krüger, Victoria Lauer, Sebastian Uebel, Karl X. Knaup, Julia Naas, Verena Höffken, Thomas Weide, Mario Schiffer, Stephanie Naas, Johannes Schödel
Journal: Kidney International (2023)

Individuals of African ancestry carrying two pathogenic variants of apolipoprotein 1 (APOL1) have a substantially increased risk for developing chronic kidney disease. The course of APOL1 nephropathy is extremely heterogeneous and shaped by systemic factors such as a response to interferon. However, additional environmental factors operating in this second-hit model have been less well defined. Here, we reveal that stabilization of hypoxia-inducible transcription factors (HIF) by hypoxia or HIF prolyl hydroxylase inhibitors activates transcription of APOL1 in podocytes and tubular cells. An active regulatory DNA-element upstream of APOL1 that interacted with HIF was identified. This enhancer was accessible preferentially in kidney cells. Importantly, upregulation of APOL1 by HIF was additive to the effects of interferon. Furthermore, HIF stimulated expression of APOL1 in tubular cells derived from the urine of an individual carrying a risk variant for kidney disease. Thus, hypoxic insults may serve as important modulators of APOL1 nephropathy.
Kidney medullary sodium chloride concentrations induce neutrophil and monocyte extracellular DNA traps that defend against pyelonephritis in vivo
Authors: Adrian Goldspink, Jessica Schmitz, Olena Babyak, Nicolas Brauns, Julia Milleck, Anne M. Breloh, Susanne V. Fleig, Katarzyna Jobin, Lisa Schwarz, Hermann Haller, Florian Wagenlehner, Jan Hinrich Bräsen, Christian Kurts, Sibylle von Vietinghoff
Journal: Kidney International (2023)
The impact of the cytoplasmic ubiquitin ligase TNFAIP3 gene variation on transcription factor NF-κB activation in acute kidney injury
Authors: Natasha M. Rogers, Nathan Zammit, Danny Nguyen-Ngo, Yassine Souilmi, Nikita Minhas, Daniel N. Meijles, Eleanor Self, Stacey N. Walters, Joanna Warren, Daniele Cultrone, Maryam El-Rashid, Jennifer Li, Tatyana Chtanova, Philip J. O’Connell, Shane T. Grey
Journal: Kidney International (2023)
Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Compensated Cirrhosis (FALCON 2): A Randomized Phase 2b Study
Authors: Manal F. Abdelmalek, Arun J. Sanyal, Atsushi Nakajima, Brent A. Neuschwander-Tetri, Zachary D. Goodman, Eric J. Lawitz, Stephen A. Harrison, Ira M. Jacobson, Kento Imajo, Nadege Gunn, Dina Halegoua-DeMarzio, Takemi Akahane, Bradly Boone, Masayuki Yamaguchi, Arkendu Chatterjee, Giridhar S. Tirucherai, Diane E. Shevell, Shuyan Du, Edgar D. Charles, Rohit Loomba
Journal: Clinical Gastroenterology and Hepatology (2023)

Pegbelfermin is a polyethylene glycol-conjugated analog of human fibroblast growth factor 21, a nonmitogenic hormone that regulates energy metabolism. This phase 2b study evaluated 48-week pegbelfermin treatment in patients with nonalcoholic steatohepatitis (NASH) with compensated cirrhosis.
A randomized-controlled trial of SOF/VEL/VOX with or without ribavirin for retreatment of chronic hepatitis C
Authors: Mohamed El-Kassas, Mohammed Emadeldeen, Mohamed Hassany, Gamal Esmat, Ahmed Ali Gomaa, Fathiya El-Raey, Stephen E. Congly, Hongqun Liu, Samuel S. Lee
Journal: Journal of Hepatology (2023)
Pegbelfermin in Patients With Nonalcoholic Steatohepatitis and Stage 3 Fibrosis (FALCON 1): A Randomized Phase 2b Study
Authors: Rohit Loomba, Arun J. Sanyal, Atsushi Nakajima, Brent A. Neuschwander-Tetri, Zachary D. Goodman, Stephen A. Harrison, Eric J. Lawitz, Nadege Gunn, Kento Imajo, Natarajan Ravendhran, Takemi Akahane, Bradly Boone, Masayuki Yamaguchi, Arkendu Chatterjee, Giridhar S. Tirucherai, Diane E. Shevell, Shuyan Du, Edgar D. Charles, Manal F. Abdelmalek
Journal: Clinical Gastroenterology and Hepatology (2023)

Pegbelfermin is a polyethlene glycol-conjugated analog of human fibroblast growth factor 21, a nonmitogenic hormone that regulates energy metabolism. This phase 2b study evaluated 48-week pegbelfermin treatment in patients with nonalcoholic steatohepatitis (NASH) and stage 3 (bridging) fibrosis.
Hepatocyte dedifferentiation profiling in alcohol-related liver disease identifies CXCR4 as a driver of cell reprogramming
Authors: Beatriz Aguilar-Bravo, Silvia Ariño, Delia Blaya, Elisa Pose, Raquel A. Martinez García de la Torre, María U. Latasa, Celia Martínez-Sánchez, Laura Zanatto, Laura Sererols-Viñas, Paula Cantallops-Vilà, Silvia Affo, Mar Coll, Xavier Thillen, Laurent Dubuquoy, Matías A. Avila, Josepmaria Argemi, Arantza Lamas Paz, Yulia A. Nevzorova, Francisco Javier Cubero, Ramon Bataller, Juan José Lozano, Pere Ginès, Philippe Mathurin, Pau Sancho-Bru
Journal: Journal of Hepatology (2023)
Loss of APOO (MIC26) aggravates obesity-related whitening of brown adipose tissue via PPARα-mediated functional interplay between mitochondria and peroxisomes
Authors: Xin Guo, Jiarui Hu, Guangxu He, Jin Chen, Yang Yang, Donglu Qin, Chenyu Li, Zhijie Huang, Die Hu, Cheng Wei, Fengjiao Wang, Bilian Yu
Journal: Metabolism (2023)
Unpaired, unsupervised domain adaptation assumes your domains are already similar
Authors: Gijs van Tulder, Marleen de Bruijne
Journal: Medical Image Analysis (2023)

Unsupervised domain adaptation is a popular method in medical image analysis, but it can be tricky to make it work: without labels to link the domains, domains must be matched using feature distributions. If there is no additional information, this often leaves a choice between multiple possibilities to map the data that may be equally likely but not equally correct. In this paper we explore the fundamental problems that may arise in unsupervised domain adaptation, and discuss conditions that might still make it work. Focusing on medical image analysis, we argue that images from different domains may have similar class balance, similar intensities, similar spatial structure, or similar textures. We demonstrate how these implicit conditions can affect domain adaptation performance in experiments with synthetic data, MNIST digits, and medical images. We observe that practical success of unsupervised domain adaptation relies on existing similarities in the data, and is anything but guaranteed in the general case. Understanding these implicit assumptions is a key step in identifying potential problems in domain adaptation and improving the reliability of the results.
A randomised-controlled trial (TARGET-C) of high vs. low target mean arterial pressure in patients with cirrhosis and septic shock
Authors: Rakhi Maiwall, Samba Siva Rao Pasupuleti, Ashini Kumar Hidam, Anupam Kumar, Harsh Vardhan Tevethia, Rajan Vijayaraghavan, Arpita Majumdar, Adarsh Prasher, Sherin Thomas, Rajendra Prasad Mathur, Guresh Kumar, Shiv Kumar Sarin
Journal: Journal of Hepatology (2023)
Assessment of longitudinal serum neutrophil extracellular trap–inducing activity in anti-neutrophil cytoplasmic antibody–associated vasculitis and glomerulonephritis in a prospective cohort using a novel bio-impedance technique
Authors: Joop P. Aendekerk, Renée Ysermans, Matthias H. Busch, Ruud O.M.F.I.H. Theunissen, Nele Bijnens, Judith Potjewijd, Jan G.M.C. Damoiseaux, Chris P. Reutelingsperger, Pieter van Paassen
Journal: Kidney International (2023)

Neutrophil extracellular traps (NET) have been implicated in the pathogenesis of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Here, we developed a novel, label-free, high-throughput bio-impedance technique to effectively measure serum NET-inducing activity. Using this technique, NET-inducing activity of serum derived from patients with AAV was assessed in a prospective cohort of 62 patients presenting with active AAV with major organ involvement. Thirty-five patients presented with new and 27 patients presented with relapsing AAV, of whom 38 had kidney and/or 31 had lung involvement. NET-inducing activity was assessed at diagnosis of active AAV (time zero), during the first 6 weeks of treatment, and after 6 months of treatment. Forty-seven patients revealed elevated NET-inducing activity at time zero. After initiation of immunosuppressive treatment, NET-inducing activity was reduced at six weeks. A subsequent increase at six months could potentially identify patients with relapsing disease (hazard ratio, 11.45 [interquartile range 1.36-96.74]). NET-inducing activity at time zero correlated with kidney function and proteinuria. Importantly, in kidney tissue, NETs co-localized with lesions typical of ANCA-associated glomerulonephritis and even correlated with systemic serum NET-inducing activity. Thus, our prospective data corroborate the importance of NET formation in AAV and ANCA-associated glomerulonephritis and the potential of longitudinal evaluation, as monitored by our novel bio-impedance assay and detailed histological evaluation.
PB1861: ACALABRUTINIB IN THE TREATMENT OF RICHTER SYNDROME
Authors: T. Byalik, N. Kokosadze, E. Paramonova, D. Semichev, A. Odzharova, A. Semenova, G. Tumyan, E. Osmanov, T. Byalik
Journal: HemaSphere (2022)

Background: Richter syndrome is a transformation of chronic lymphocytic leukemia into DLBCL, occurring in about 2-15% of patients (pts) with CLL. These patients have a very poor prognosis with an unsatisfactory response to immunochemotherapy (R-XT) and a short overall survival. B-cell receptor signaling through Bruton tyrosine kinase (BTK) is one of the essential growth pathways for CLL. Acalabrutinib (highly selective BTK inhibitor) has shown significant efficacy in relapsed/refractory and untreated CLL. Aims: improving the results of treatment of patients with Richter syndrome Methods: we reported 4 cases of Richter syndrome treated with acalabrutinib + R-СТ. Results: Table 1 shows the characteristics of 4 CLL pts who developed biopsy-proven DLBCL. The median time to transformation from CLL was 40,75 months (range 4-66). Clonality was not available testing in any pts. At the time of transformation, 2 pts were initially treated with R-CHOP with a suboptimal response, then acalabrutinib was added, 1 pt received 6 cycles of R-CHOP+ acalabrutinib and 1pt - 5 cycles R-CVP + acalabrutinib. The overall response (OR) was 75%:1 pt had a CR and 2 pts - PR. The pts who achieved OR are currently receiving acalabrutinib, 1 pt had progression of DLBCL after 15 months of acalabrutinib therapy. Acalabrutinib was well-tolerated; no patient required discontinuation as a result of adverse events. At the time of CLL diagnosis (table1) - Age, y 75 28 64 34 Sex M F M F Rai st. II II II II CLL therapyEfficacy Rituximab 2013 to 2015.CR none 6-G-FC in 2016 CR 6 FCR in 2020CR Time from CLL therapy to RS 66m 45m 48m 4m Localization of DLBCL Peripheral, retroperitoneal lymph nodes, stomach Lymph nodes, nasal sinuses, upper palate Retroperitoneal lymph nodes, colon Tumor of the tongue root DLBCL subtype GCB Non-GCB Non-GCB Non-GCB At the time of DLBCL diagnosis (Table 1- continuation) - 1 2 3 4 Age, y 82 32 69 35 WBC ×109/L 5,53 х10х9/L 6,23х10х9/L 10,25х10х9/L 0,840 х10х9/L Hemoglobin, g/dL 12,4 11,6 10,7 6,6 Platelet count ×109/L 178,0 294,0 120,0 41,0 LDH, U/L 322 196 410 317 IGHV mutation status It is not possible to establish Unmutated Unmutated It is not possible to establish FISH Normal Normal Normal Normal Mutation TP53 No mutations. No mutations No mutations No mutations Mutation NOTCH1 - Mutation c7544 No mutation No mutation RS prognosis score 2 (Intermediate) 1 (Low) 2 (Intermediate) 1 (Low) Duration of acalabrutinib therapy (mon) 15 12 15 5 Best response PR CR Clinical benefit PR Status at most recent follow-up Аcalabrutinib therapy continues Аcalabrutinib therapy continues Death Аcalabrutinib therapy continues Summary/Conclusion: our experience with these patients suggests that acalabrutinib in combination with immunochemotherapy has potential as a novel therapeutic approach for patients with Richter syndrome.
Lymphocytic oesophagitis: clinicopathological aspects of an emerging condition
Authors: Salima Haque, Robert M Genta
Journal: Gut (2011)

<h3>Objective</h3> Lymphocytic oesophagitis (LyE) has been reported in small series, but no consistent clinical correlations have emerged. The authors sought to determine the prevalence of LyE in a large population and define demographic, endoscopic and clinical findings associated with this condition. <h3>Design</h3> In a pilot study, the authors established and disseminated criteria for the histopathological diagnosis of LyE to a group of gastrointestinal pathologists. Eighteen months later the authors reviewed cases with this diagnosis, collected demographic, clinical and endoscopic data, and compared them with patients with either eosinophilic oesophagitis (EoE) or normal oesophageal biopsies. The authors also determined the density of oesophageal lymphocytes in normal controls and in adults with established Crohn9s disease. <h3>Results</h3> There were 129 252 unique patients: 40 665 had normal mucosa (median age 55 years; 32% men); 3745 had EoE (median age 43 years; 66% men). A diagnosis of LyE was made in 119 patients (median age 63 years, 40% men). Dysphagia was as common in these patients as in those with EoE (53% vs 63%; ns); gastro-oesophageal reflux disease —the most common complaint in patients with normal biopsies (37%)—was low in both the LyE and the EoE groups (18% vs 19%, ns). EoE was suspected in one-third of the patients. <h3>Conclusion</h3> LyE was detected in ∼0.1% of patients with oesophageal biopsies. The clinical and endoscopic characteristics of LyE and EoE overlap considerably; however, LyE affects predominantly older women. Although the precise clinical significance of oesophageal lymphocytic infiltrates remain to be defined, their association with dysphagia and possibly motility disorders warrants further investigations.
Systemic therapy for atopic dermatitis
Authors: D. Simon, T. Bieber
Journal: Allergy (2013)

Abstract Systemic therapy for atopic dermatitis ( AD ) is indicated in patients with severe disease refractory to adequate topical treatment. Currently available drugs aim to decrease inflammation by suppressing and/or modulating immune responses and thus may indirectly improve skin barrier function, resulting in a decrease in clinical signs and symptoms in particular pruritus. Before considering systemic treatment, patient adherence to topical treatment including skin care has to be ensured. The selection of the drug depends on the disease severity, localization, complications, concomitant diseases, and age of the patient, but also on their availability and costs as well as the doctor's experience. Bearing in mind the potential risk of resistance, systemic therapy with antibiotics should be exclusively considered in clinically manifest infections such as in children. Here, we review recently published clinical trials and case reports on systemic therapy of pediatric and adult patients with AD to draw conclusions for clinical practice. Although AD is a common disease, controlled clinical studies investigating the efficacy of systemic drugs are scarce, except for cyclosporine, which has been approved for the therapy of severe AD .
Phase III Study of the Eastern Cooperative Oncology Group (ECOG 2597): Induction Chemotherapy Followed by Either Standard Thoracic Radiotherapy or Hyperfractionated Accelerated Radiotherapy for Patients With Unresectable Stage IIIA and B Non–Small-Cell Lung Cancer
Authors: Chandra P. Belani, Wei Wang, David H. Johnson, Henry Wagner, Joan Schiller, Michael Veeder, Minesh Mehta
Journal: Journal of Clinical Oncology (2005)

Purpose To compare once-daily radiation therapy (qdRT) with hyperfractionated accelerated radiation therapy (HART) after two cycles of induction chemotherapy. Patients and Methods Eligible patients were treatment naive, and had stage IIIA and B unresectable non-small-cell lung cancer, Eastern Cooperative Oncology Group performance status 0/1, and normal organ function. Induction chemotherapy consisted of two cycles of carboplatin area under time-concentration curve 6 mg/mL · min plus paclitaxel 225 mg/m 2 on day 1. RT consisted of arm 1 (qdRT), 64 Gy (2 Gy/d), versus arm 2 (HART), 57.6 Gy (1.5 Gy tid for 2.5 weeks). A total of 388 patients were needed to detect a 50% increase in median survival from 14 months of qdRT to 21 months of HART; accrual was not achieved and the study closed prematurely. Results Of 141 patients enrolled, 83% were randomly assigned after chemotherapy to qdRT (n = 59) or HART (n = 60). Median survival was 20.3 and 14.9 months for HART and qdRT, respectively (P = .28). Overall response was 25% and 22% for HART and qdRT, respectively (P = .69). Two- and 3-year survival was 44% and 34% for HART, and 24% and 14% for qdRT, respectively. Grade ≥ 3 toxicities included esophagitis in 14 v nine patients, and pneumonitis in 0 v 6 patients for HART and qdRT, respectively. Any subsequent trials of the HART regimen must address the issues that led to early closure, including slow accrual, logistics of HART, mucosal toxicity, and the fact that concurrent chemoradiotherapy now seems more effective than sequential treatment. Conclusion After two cycles of induction chemotherapy with carboplatin-paclitaxel, HART is feasible with an acceptable toxicity profile. Although statistical significance was not achieved and the study closed early, there was a positive statistical trend suggesting a survival advantage with the HART regimen.
BARRETT'S ESOPHAGUS AND ADENOCARCINOMA
Authors: B J Reid, W M Weinstein
Journal: Annual Review of Medicine (1987)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Recent Advances in Assembly of Complex Plant Genomes
Authors: Weilong Kong, Yibin Wang, Shengcheng Zhang, Jiaxin Yu, Xingtan Zhang
Journal: Genomics Proteomics & Bioinformatics (2023)

Abstract Over the past 20 years, tremendous advances in sequencing technologies and computational algorithms have spurred plant genomic research into a thriving era with hundreds of genomes decoded already, ranging from those of nonvascular plants to those of flowering plants. However, complex plant genome assembly is still challenging and remains difficult to fully resolve with conventional sequencing and assembly methods due to high heterozygosity, highly repetitive sequences, or high ploidy characteristics of complex genomes. Herein, we summarize the challenges of and advances in complex plant genome assembly, including feasible experimental strategies, upgrades to sequencing technology, existing assembly methods, and different phasing algorithms. Moreover, we list actual cases of complex genome projects for readers to refer to and draw upon to solve future problems related to complex genomes. Finally, we expect that the accurate, gapless, telomere-to-telomere, and fully phased assembly of complex plant genomes could soon become routine.